safety and efficacy of donor t-lymphocytes depleted ex vivo of host alloreactive t-cells (atir) in patients with a hematologic malignancy who received a hematopoietic stem cell transplantation from a haploidentical donor

Conditions: Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndrome

Summary: the purpose of this study is to determine whether atir is safe and effective in reducing transplant-related mortality and improving overall survival, when infused in patients with a hematologic malignancy following a t-cell depleted stem cell graft from a related haploidentical donor.

study cr-air-007 is an exploratory, open-label, multicenter study. after signing informed consent, patients will receive a hematopoietic stem cell transplantation (hsct) from a related, haploidentical donor, followed by infusion with atir between 28 and 32 days after the hsct (or later if required by the patient's medical condition). patients will receive atir as a single infusion at a dose of 2x10e6 viable t-cells/kg. all patients treated with atir will be followed up until 12 months after the hsct. assessments will be performed at weekly visits from the day of atir infusion until 8 weeks after atir infusion, at monthly visits from 3 until 6 months after the hsct, every 2 months from 6 until 12 months after the hsct, and every 6 months from 12 until 24 months after the hsct.

Eligibility criteria:
inclusion criteria: * any of the following hematologic malignancies: a) acute myeloid leukemia (aml) in first remission with high-risk features or in second or higher remission b) acute lymphoblastic leukemia (all) in first remission with high-risk features or in second or higher remission c) myelodysplastic syndrome (mds): transfusion-dependent, or intermediate or higher revised international prognostic scoring system (ipss-r) risk group * eligible for haploidentical stem cell transplantation according to the investigator exclusion criteria: * availability of a suitable matched related or unrelated donor following a donor search * in second or higher remission with the previous remission having lasted less than 6 months * diffusing capacity for carbon monoxide (dlco) \< 50% predicted * left ventricular ejection fraction \< 50% (evaluated by echocardiogram or multiple gated acquisition \[muga\]) * aspartate aminotransferase (ast) \> 2.5 x upper limit of normal (uln)(ctcae grade 2) * bilirubin \> 1.5 x uln (ctcae grade 2) * creatinine clearance \< 50 ml/min (calculated or measured) * positive test for human immunodeficiency virus (hiv) * positive pregnancy test (women of childbearing age only) * prior allogeneic stem cell transplantation using stem cells from a matched sibling donor, a matched unrelated donor, a haploidentical donor, or a cord blood donor * prior autologous stem cell transplantation * stay at intensive care unit for more than 2 months in the preceding 12 months * estimated probability of surviving less than 3 months * known allergy to any of the components of atir (e.g., dimethyl sulfoxide) * any other condition which, in the opinion of the investigator, makes the patient ineligible for the study donor inclusion criteria * haploidentical family donor with 2 to 3 mismatches at the human leukocyte antigen (hla)-a, -b and/or -dr loci of the unshared haplotype * male or female, age ≥ 16 and ≤ 75 years * eligible for donation according to the transplantation center donor exclusion criteria * positive viral test for hiv-1, hiv-2, hepatitis b virus (hbv), hepatitis c virus (hcv), treponema pallidum, human t-lymphotropic virus (htlv)-1\*, htlv-2\*, or west nile virus (wnv)\* (if tested) (\* at canadian centers only) * positive pregnancy test or nursing (women of childbearing age only)

Keywords: haploidentical stem cell transplantation graft-versus-host disease immune reconstitution alloreactive t-cells photodepletion photodynamic treatment th9402 transplant-related mortality hematologic malignancy